The objectives of the proposed research are to identify the mechanism by which Aleutian disease virus produces a persistent infection in mink and to characterize the infectious agent of scrapie. When Aleutian disease virus is isolated from persistently infected mink, it will replicate in cell culture only at a temperature considerably less than the body temperature of mink. After cell culture passage, the virus can replicate at higher temperatures. We will assess the temperature-sensitivity of additional isolates of this virus. Culture-adapted virus which will replicate at the body temperature of mink will be inoculated into mink to find if temperature-sensitive virus is re-selected when the mink become persistently infected. Aleutian disease virus cannot be neutralized by mink antibody. The reason for the lack of neutralization will be studied using antiviral antibody prepared in other species and monodisperse virus separated from membrane fragments. The causative agent of scrapie appears not to be a naked nucleic acid (viroid). Experiments attempting to reconstitute scrapie infectivity will combine nucleic acid from the brains of scrapie-affected mice with normal mouse brain cellular and membrane materials. If successful, such experiments could indicate the type of nucleic acid, if any, in the scrapie agent.